Structure and biological function
WNT3A is a secreted glycoprotein and belongs to the WNT family. Members of this family can interact with cell membrane receptors, thus playing a role in autocrine regulations and paracrine signaling. WNT3A is expressed in placenta at moderate levels, as well as in lung, spleen and prostate at low levels. The canonical sequence of WNT3A consists of 352 amino acids (aa) and has a mass of 39.365 kDa. It is rich in cysteine and forms many disulfide bonds from cysteine residues. At aa 87 and aa 298 glycosylation appears, since N-Acetylglucosamine is covalently attached to asparagine. At position aa 209 WNT3A is covalently lipidated at a conserved serine residue resulting in strong hydrophobic properties of the molecule. Therefore, in its physiological form it constitutes a soluble complex with afamin, which functions as a carrier for hydrophobic molecules in body fluids and is essential for the activity and solubility of WNT3A. WNT3A plays important roles in cell growth and differentiation, embryonic development, neural development, immune regulation, bone formation and carcinogenesis.
Involvement in diseases :
Elevated expression of WNT3A has been found in prostate-, breast- and hepatocellular cancer tissue. Accumulating evidence has suggested that WNT3A promotes or suppresses tumor progression via the canonical Wnt signaling pathway depending on cancer type. A vast number of studies on the role of this molecule have been and are still performed (Sha H et al., Chin J Cancer. 2015;34(12):554-62). WNT3A remains to be a hot topic in cancer research
Ankylosing spondylitis (AS) is associated with both pathologic formation of new bone and enhanced bone resorption. Thus it is not surprising that molecules involved in either of those biological pathways may be valuable biomarkers to study this disease. It is well known, that the Wnt signaling pathway plays an essential role in bone remodeling (and therefore in AS) and so might the Wnt-protein family members and their antagonists, which has been proven by finding elevated levels of DKK-1 and WNT3A in AS patients (Klingberg E et al., Ann Rheum Dis. 2012;71:A64)
A variety of studies have been investigating Wnt-signaling in multiple myeloma (MM) because secretion of Wnt signaling inhibitors by the tumor cells contributes to MM-related bone resorption and disease progression. A lot of focus has been laid on studying regulators of the wnt-pathway (e.g. DKKs, sFRPs) as biomarkers in MM but there are only few data about the importance of WNT3A as marker in MM yet (Qiang YW et al., Blood. 2008;112(2):374-382.)
As wnt-signaling is the center piece of bone remodeling, Wnt-family members play a major role in osteoporosis (OP). Interestingly, WNT3A seems to mediate the beneficial effects of mechanical loading on bone quality (Li X et al. , FASEB J. 2019 Aug;33(8):8913-8924)
A number of studies have shown, that WNT3A has regenerative effects on spinal cord injuries (Yin ZS et al. Neurol Res. 2008 Jun;30(5):480-6). This makes WNT3A not only a therapeutically interesting molecule but also a potential biomarker for cell culture and animal models used for studying repair of such injuries